KSU MEDICAL JOURNAL KAHRAMANMARAŞ SÜTÇÜ İMAM ÜNİVERSİTESİ TIP FAKÜLTESİ DERGİSİ KSU MEDICAL JOURNAL. Yıl Year e-issn: ISSN:

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KAHRAMANMARAŞ SÜTÇÜ İMAM ÜNİVERSİTESİ

TIP FAKÜLTESİ DERGİSİ

Cilt / Volume: 15 Sayı / Number: 1

Yıl Year 2020

KSU MEDICAL JOURNAL

ISSN: 1303 - 6610 e-ISSN: 2547 - 9598

KSU MEDICAL JOURNAL

Cilt/ Volume:15 Sayı/ Number:3

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http://tipfakultesi.ksu.edu.tr/

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Hatice Araç

Grafik Tasarım ve Dizgi

H

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Kurulu DERGİ DANIŞMA

Dergi Sahibi Prof.Dr. Niyazi CAN

Yayın Kurulu Baş Editör

Doç. Dr. Özkan GÜNGÖR (KSÜ Tıp Fakültesi)

Editörler Doç.Dr.İsrafil ORHAN

(KSÜ Tıp Fakültesi) Doç.Dr.Orçun ALTUNÖREN

(KSÜ Tıp Fakültesi) Doç.Dr.Selçuk NAZİK

(KSÜ Tıp Fakültesi) Doç.Dr. Fatih Mehmet YAZAR

(KSÜ Tıp Fakültesi)

Doç.Dr. Ramazan Azim OKYAY (KSÜ Tıp Fakültesi)

Dr.Öğretim Üyesi Tuba Tülay KOCA (KSÜ Tıp Fakültesi)

Yabancı Dil Editörü

Dr.Öğretim Üyesi Tuba Tülay KOCA (KSÜ Tıp Fakültesi)

İstatistik Editörü Dr. Öğr. Üyesi Adem DOĞANER

(KSÜ Tıp Fakültesi) Grafik Tasarım ve Dizgi

Hatice ARAÇ Sekreter Mustafa Türker Yazışma Adresi:

KSÜ Tıp Fakültesi Dekanlık Dergi Editörlüğü 46100 Kahramanmaraş

Mail:

ozkan.gungor@yahoo.com ogungor@ksu.edu.tr

Tel: 0344 300 34 08 Faks: 0344 300 34 09

Bülent KANTARÇEKEN (Kahramanmaraş)

Perihan ÖZTÜRK (Kahramanmaraş)

Sena ULU (Afyonkarahisar)

İsmail KOÇYİĞİT (Kayseri)

Zafer YÜKSEL (Kahramanmaraş)

Özgür ÖZMEN (Erzurum)

Behice KURTARAN (Adana)

Mehmet BOŞNAK (Kahramanmaraş)

Şeyda ÇANKAYA (Alanya)

Cengiz DİLBER (Kahramanmaraş)

Mehmet Muhittin YALÇIN (Ankara)

Salih TAŞKIN (Ankara)

Kamile GÜL (Kahramanmaraş)

Kenan TOPAL (Adana)

Mehmet BEKERECİOĞLU (Kahramanmaraş) Ramazan GÜNEŞAÇAR (Alanya)

Vedat NACİTARHAN (Kahramanmaraş)

Erhan TATAR (İzmir)

Deniz Cemgil ARIKAN (Kahramanmaraş)

Sibel EYİGÖR (İzmir)

Fatih TEMİZ (Kahramanmaraş)

Fatma Özlem ORHAN (Kahramanmaraş)

Osman CELBİŞ (Malatya)

Juan Jesus CARRERO (İsveç)

Jamal MUSAYEV (Azerbaycan)

Prem CHARLES (Hindistan)

Anar İBRAHİMOV (Azerbaycan)

Müşfiq ORUCOV (Azerbaycan)

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AMAÇ

Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fa- kültesi Dergisi bilimsel bir dergi olup, tıbbın çeşitli alanlarında araştırma makaleleri, olgu sunumları ve derlemeleri yayınlar

KAPSAM

Dergi Kahramanmaraş Sütçü İmam Üniversite- si (KSÜ) Tıp Fakültesinin yayın organı olup, ulusal ve uluslar arası tüm tıbbi kurum ve personele ulaşmayı he- deflemektedir. Derginin yayın prensipleri, bağımsız, ön yargısız ve çift-kör hakemlik ilkelerine dayanmaktadır.

Yayın Kurulu, Uluslararası Tıp Dergisi Editörleri Kon- seyi (ICMJE) ve Yayın Etik İlkeleri Komisyonu (COPE) ilkeleri çerçevesinde çalışır.

Yayın aşamasında ve kabul sonrasında yazarlardan hiç- bir ücret talep edilmemektedir. KSÜ Tıp Fakültesi Der- gisi yılda 3 sayı olmak üzere 4 ayda bir (Nisan, Ağustos, Aralık) çıkar. Derginin yazı dili Türkçe ve İngilizcedir.

AIM

KSU Medical Journal is a scientific journal which aims to publish original articles, case reports and reviews on different fields of medicine.

SCOPE

KSU Medical Journal is the official journal of Kahra- manmaraş Sütçü İmam University Faculty of Medicine and aims to reach all national and international medical institutions and staff. It has the highest ethical and scientific standards and has no commercial concerns in publishing manuscript. The publication principles of the journal are based on the principles of independent, peer-review and double-blinded refereeing. Editorial Board of the KSU Medical Journal complies with the criteria of the International Council of Medical Journal Editors (ICMJE), and Committee on Publication Ethics (COPE).

No fee is requested from the authors at the publishing stage and after acceptance. Journal is published every 4 months, 3 times (April, August, December) a year. The publication language of the journal is Turkish and English.

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YAYIN KURALLARI

Yayınlanmak için gönderilen makalelerin daha önce başka bir yerde yayınlanmamış veya yayınlanmak üze- re gönderilmemiş olması gerekir. Eğer makalede daha önce yayınlanmış; alıntı yazı, tablo, resim vs. mevcut ise makale yazarı, yayın hakkı sahibi ve yazarlarından yazılı izin almak ve bunu makalede belirtmek zorun- dadır. Bilimsel toplantılarda sunulan özetler, makalede belirtilmesi koşulu ile kabul edilir. Dergiye gönderilen makale biçimsel esaslara uygun ise, editör ve en az yurt içi-yurt dışı iki danışmanın incelemesinden geçip, ge- rek görüldüğü takdirde, istenen değişiklikler yazarlarca yapıldıktan sonra yayınlanır.

BİLİMSEL SORUMLULUK

Tüm yazarların gönderilen makalede akademik-bilimsel olarak doğrudan katkısı olmalıdır. Yazar olarak belirlenen isimler çalışmayı planlanması, yapılması, yazılması veya revize edilmesi aşamasında görev al- malıdırlar. Bütün yazarlar makalenin son halini kabul etmelidirler. Makalelerin bilimsel kurallara uygunluğu yazarların sorumluluğundadır.

ETİK SORUMLULUK

Dergi, “İnsan” öğesinin içinde bulunduğu tüm çalışma- larda Helsinki Deklerasyonu Prensipleri’ne uygunluk (Web sayfası erişim adresi: http:// www.wma.net/en/30publicati- ons/10policies/b3/ index.html ) ilkesini kabul eder. Bu tip çalışmaların varlığında yazarlar, makalenin “Gereç Ve Yön- temler” bölümünde bu prensiplere uygun olarak çalışmayı yaptıklarını, kurumlarının etik kurullarından ve çalışmaya katılmış insanlardan “Bilgilendirilmiş olur” (Informed Con- sent) aldıklarını belirtmek zorundadır.

Çalışmada “Hayvan” öğesi kullanılmış ise yazarlar, makalenin “Gereç ve Yöntemler” bölümünde Guide for the Care and Use of Laboratory Animals ( Web sayfası erişim adresi: www.nap. edu/catalog/5140.html ) prensipleri doğrultusunda çalışmalarında hayvan haklarını koruduklarını ve kurumlarının etik kurullarından onay aldıklarını belirtmek zorundadır.

Eğer makalede direkt-indirekt ticari bağlantı veya çalışma için maddi destek veren kurum mevcut ise yazarlar; kullanılan ticari ürün, ilaç, firma ile ticari hiçbir ilişkisinin olmadığını ve varsa nasıl bir ilişkisinin oldu- ğunu (konsültan, diğer anlaşmalar) bildirmek zorun- dadır. Makalelerin etik kurallara uygunluğu yazarların sorumluluğundadır.

PUBLICATION GUIDELINES

Articles are accepted for publication on the condi- tion that they are original, are not under consideration by another journal, or have not been previously published. Direct quotations, tables, or illustrations that have appeared in copyrighted material must be accompanied by written permission for their use from the copyright owner and authors.

All articles are subject to review by the editors and referees. Acceptance is based on significance, and origi- nality of the material submitted. If the article is accepted for publication, it may be subject to editorial revisi- ons to aid clarity and understanding without changing the data presented.

SCIENTIFIC RESPONSIBILITY

All authors should have contributed to the article directly either academically or scientifically. All per- sons designated as authors should contribute planning, performing, writing or reviewed of manuscript. All authors should approve the final version. It is the authors’

responsibility to prepare a manuscript that meets scientific criterias.

ETHICAL RESPONSIBILITY

The Journal adheres to the principles set forth in the Helsinki Declaration (http://www. wma.net/en/30pub- lications/10policies/b3/ index. html) and holds that all reported research involving “Human beings” conducted in accordance with such principles. Reports describing data obtained from research conducted in humanpar- ticipants must contain a statement in the Materıal And Methods section indicating approval by the institutio- nal ethical review board and affirmation that Informed Consent was obtained from each participant.

All papers reporting experiments using animals must include a statement in the Materıal and Methods section giving assurance that all animals have received humane care in compliance with the Guide for the Care and Use of Laboratory Animals (www.nap.edu/catalog/5140.html) and indicating approval by the institu- tional ethical review board. If the proposed publication concerns any commercial product, the author must include in the cover letter a statement indicating that the author(s) has (have) no financial or other interest in the product or explaining the nature of any relation (including consultancies) between the author(s) and the manufacturer or distributor of the product. It is the authors’ responsibility to prepare a manuscript that meets ethical criteria.

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İSTATİSTİKSEL DEĞERLENDİRME

Tüm retrospektif, prospektif ve deneysel araştırma makaleleri biyoistatistiksel olarak değerlendirilmeli ve uygun plan, analiz ve raporlama ile belirtilmelidir

YAZIM DİLİ YÖNÜNDEN DEĞERLENDİRME

Derginin yayın dili Türkçe ve İngilizce’dir. Makale- lerde Türk Dil Kurumu’nun Türkçe sözlüğü veya www.

tdk.org/dergi adresi, ayrıca Türk Tıbbi Derneklerinin kendi branşlarına ait terimler sözlüğü esas alınmalıdır.

İngilizce makaleler ve İngilizce özetler, dergiye gönde- rilmeden önce dil uzmanı tarafından değerlendirilme- lidir.

MAKALE GÖNDERMEK İÇİN

Tüm yazılar editorial ofise http://dergipark. gov.tr/

ksutfd URL adresinden online olarak gönderilmelidir.

Detaylı bilgi dergi web sitesinden ayrıntılı olarak sağ- lanabilir. Ayrıca gönderilmiş olan makalelerdeki yazım ve dilbilgisi hataları, makalenin içeriğine dokunmadan, redaksiyon komitemiz tarafından düzeltilmektedir.

YAYIN HAKKI

1976 Copyright Act’e göre, yayınlanmak üzere kabul edilen yazıların her türlü yayın hakkı dergiyi yayınla- yan kuruma aittir. Yazılardaki düşünce ve öneriler tü- müyle yazarların sorumluluğundadır.

STATISTICAL EVALUATION

All retrospective, prospective and experimental research articles must be evaluated in terms of biostatics and it must be stated together with appropriate plan, analysis and report. p values must be given clearly in the manuscripts

EVALUATION OF THE WRITING LANGUAGE

The official languages of the Journals are Turkish and English. Manuscripts and abstracts in English must be checked for language by an expert. It is the authors’

responsibility to prepare a manuscript that meets spel- ling and grammar rules

FOR SUBMITTING AN ARTICLE

All manuscripts and editorial correspondence must be submitted online to the editorial Office http://dergipark.gov.tr/ksutfd. Detailed submission information is provided at the online editorial office web site.

COPYRIGHT STATEMENT

In accordance with the Copyright Act of 1976, the publisher owns the copyright of all published articles.

Statements and opinions expressed in the published material herein are those of the author(s).

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YAZI ÇEŞİTLERİ

Dergiye yayınlanmak üzere gönderilecek yazı çeşit- leri şu şekildedir:

Orijinal Araştırma: Kliniklerde yapılan prospek- tif-retrospektif ve her türlü deneysel çalışmalar yayın- lanabilmektedir.

Yapısı:

Özet: Ortalama 200-250 kelimeden oluşan Türkçe ve İngilizce bölümlü özet olmalıdır [amaç (objective), gereç ve yöntemler (material and methods), bulgular (results) ve sonuç (conclusion)]

Giriş

Gereç ve Yöntemler Bulgular

Tartışma Teşekkür Kaynaklar Derleme:

Doğrudan veya davet edilen yazarlar tarafından ha- zırlanır. Tıbbi özellik gösteren her türlü konu için son tıp literatürünü de içine alacak şekilde hazırlanabilir.

Yazarın o konu ile ilgili basılmış yayınlarının olması özellikle tercih nedenidir.

Yapısı:

Özet (Ortalama 200-250 kelime, bölümsüz, Türkçe ve İngilizce)

Konu ile ilgili başlıklar Kaynaklar

Olgu Sunumu: Nadir görülen, tanı ve tedavide fark- lılık gösteren makalelerdir. Yeterli sayıda fotoğraflarla ve şemalarla desteklenmiş olmalıdır.

Yapısı:

Özet (ortalama 200-250 kelime; bölümsüz; Türkçe ve İngilizce)

Giriş

Olgu Sunumu Tartışma Kaynaklar

CATEGORIES OF ARTICLES

The Journal publishes the following types of articles:

Original Research Articles: Original prospective or retrospective studies of basic or clinical investigations in areas relevant to medicine.

Content:

Abstract (200-250 words; the structured abstract contain the following sections: objective, material and methods, results, conclusion; English and Turkish)

Introduction

Material and Methods Results

Discussion

Acknowledgements References

Review Articles:

The authors may be invited to write or may submit a review article. Reviews including the latest medical literature may be prepared on all medical topics. Authors who have published materials on the topic are prefer- red.

Content:

Abstract (200-250 words; without structural divisions; English and Turkish)

Titles on related topics References

Case Reports: A unique unreported manifestati- on or treatment of a known disease process, or unique unreported complications of treatment regimens. They should include an adequate number of photos and figures.

Content:

Abstract (average 200-250 words; without structural divisions; English and Turkish)

Introduction Case report Discussion References

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YAZIM KURALLARI

Dergiye yayınlanması için gönderilen makalelerde aşağıdaki biçimsel esaslara uyulmalıdır. Makale, PC uyumlu bilgisayarlarda Microsoft Word programı ile yazılmalıdır.

KISALTMALAR:

Kelimenin ilk geçtiği yerde parantez içinde verilir ve tüm metin boyunca o kısaltma kullanılır.

Başlıkta kesinlikle kısaltma kullanılmaz. Özette ise herkes tarafından kabul edilen kısaltmalar kullanılabi- lir (ör: MR, TSH..)

ŞEKİL, RESİM, TABLO ve GRAFİKLER:

Şekil, resim, tablo ve grafiklerin metin içinde geçtiği yerler ilgili cümlenin sonunda belirtilmelidir.

Şekil, resim, tablo ve grafiklerin açıklamaları makale sonuna eklenmelidir.

Şekil, resim/fotoğraflar ayrı birer .jpg veya .gif dos- yası olarak (pixel boyutu yaklaşık 500x400, 8 cm eninde ve 300 çözünürlükte taranarak) gönderilmelidir.

Kullanılan kısaltmalar şekil, resim, tablo ve grafiklerin altındaki açıklamada belirtilmelidir

Daha önce basılmış şekil, resim, tablo ve grafik kul- lanılmış ise yazılı izin alınmalıdır ve bu izin açıklama olarak şekil, resim, tablo ve grafik açıklamasında belirtilmelidir.

Resimler/fotoğraflar renkli, ayrıntıları görülecek de- recede kontrast ve net olmalıdır.

MANUSCRIPT PREPARATION

Authors are encouraged to follow the following principles before submitting their material. The article should be written in computers with Microsoft Word.

ABBREVATIONS:

Abbreviations that are used should be defined in pa- renthesis where the full word is first mentioned. Abbre- viation must not be used in title. Abbreviation accepted by everyone are used in abstract (MR, TSH...)

FIGURES, PICTURES, TABLES and GRAPHICS:

All figures, pictures, tables and graphics should be cited at the end of the relevant sentence.

Explanations about figures, pictures, tables and graphics must be placed at the end of the article.

Figures, pictures/photographs must be added to the system as separate .jpg or .gif files (approximately 500x400 pixels, 8 cm in width and scanned at 300 re- solution).

All abbreviations used, must be listed in explanation which will be placed at the bottom of each figure, pictu- re, table and graphic.

For figures, pictures, tables and graphics to be reproduced relevant permissions need to be provided.

This permission must be mentioned in the explanation.

Pictures/photographs must be in color, clear and with appropriate contrast.

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KAPAK SAYFASI:

Makalenin başlığı (Türkçe ve İngilizce), kısa başlık (Türkçe ve İngilizce) tüm yazarların ad-soyadları, akademik ünvanları, kurumları, iş telefonu-GSM, e-posta ve yazışma adresleri belirtilmelidir. Makale daha önce tebliğ olarak sunulmuş ise tebliğ yeri ve tarihi belirtilmelidir.

ÖZETLER:

Yazı Çeşitleri bölümünde belirtilen şekilde hazırla- narak, makale metni içerisine yerleştirilmelidir.

ANAHTAR KELİMELER:

• En az 3 adet, Türkçe ve İngilizce yazılmalıdır.

• İngilizce anahtar kelimeler “Medical Subject Hea- dings (MeSH)”e uygun olarak verilmelidir

(Bkz: www.nlm.nih.gov/mesh/MBrowser. html).

• Türkçe anahtar kelimeler MeSH terimlerinin ay- nen çevirisi olmalıdır. Bu yüzden anahtar kelimelerin, Türkiye Bilim Terimleri arasından seçilmesi gerekmek- tedir. Yazarlar bilgilendirme açısından “http://www.bi- limterimleri.com/ adresini ziyaret edebilirler.

TEŞEKKÜR:

Eğer çıkar çatışması, finansal destek, bağış ve diğer bütün editöryal (istatistiksel analiz, İngilizce/ Türkçe değerlendirme) ve/veya teknik yardım varsa, metnin sonunda sunulmalıdır.

KAYNAKLAR:

Kaynaklar makalede geliş sırasına göre yazılmalı ve metinde cümle sonunda noktalama işaretlerinden he- men önce paragraf içerisinde belirtilmelidir. Makalede bulunan yazar sayısı 6 veya daha az ise tüm yazarlar belirtilmeli, 7 veya daha fazla ise ilk 6 isim yazılıp “et al” eklenmelidir. Türkçe kaynaklarda “ve ark.” eklenmelidir. Kaynak yazımı için kullanılan format Index Me- dicus’ta belirtilen şekilde olmalıdır (Bkz: www.icmje.

org). Kişisel deneyimler ve basılmamış yayınlar kaynak olarak gösterilemez.

Kaynakların yazımı için örnekler (Noktalama işa- retlerine lütfen dikkat ediniz):

Makale için;

Yazar(lar)ın soyad(lar)ı ve isim(ler)inin başharf(ler)i, makale ismi, dergi ismi, yıl, cilt, sayfa no’su belirtilmelidir.

Örnek: Gungor O, Guzel FB, Sarica MA, Gungor G, Ganidagli B, Yurttutan N et al. Ultrasound Elastog- raphy Evaluations in Patient Populations With Various Kidney Diseases. Ultrasound Q. 2019;35(2):169-172.

TITLE PAGE:

A concise, informative title and short title (English and Turkish), should be provided. All authors should be listed with academic degrees, affiliations, addresses, office and mobile telephone and fax numbers, and e-mail and postal addresses. If the study was presented in a congress, the author(s) should identify the date/

place of the congress of the study presented.

ABSTRACT:

The abstracts should be prepared in accordance with the instructions in the “Categories of Articles” and placed in the article file.

KEYWORDS:

• They should be minimally three, and should be written English.

• The words should be separated by semicolon (;), from each other.

• Key words should be appropriate to “Medical Subject Headings (MESH)”(Look: www.nlm. nih.gov/

mesh/MBrowser.html).

ACKNOWLEDGEMENTS:

Conflict of interest, financial support, grants, and all other editorial (statistical analysis, language editing) and/or technical asistance if present, must be presented at the end of the text.

REFERENCES:

References in the text should be numbered as supersc- ript numbers and listed serially according to the order of mentioning on a separate page, doublespaced, at the end of the paper in numerical order. All authors should be listed if six or fewer, otherwise list the first six and add the et al. Journal abbreviations should conform to the style used in the Cumulated Index Medicus (please look at: www.

icmje.org). Declarations, personal experiments, unpublis- hed papers, thesis cannot be given as reference.

Examples for writing references (please give attenti- on to punctuation):

Format for journal articles; initials of author’s names and surnames, titles of article, journal name, date, volume, number, and inclusive pages, must be indicated.

Example: Gungor O, Guzel FB, Sarica MA, Gungor G, Ganidagli B, Yurttutan N et al. Ultrasound Elastog- raphy Evaluations in Patient Populations With Various Kidney Diseases. Ultrasound Q. 2019;35(2):169-172.

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Kitap için;

Yazar(lar)ın soyad(lar)ı ve isim(ler)inin başharf(ler) i, bölüm başlığı, editörün( lerin) ismi, kitap ismi, ka- çıncı baskı olduğu, şehir, yayınevi, yıl ve sayfalar belirtilmelidir.

Türkçe kitaplar için;

Tür A. Emergency airway management and endot- racheal intubation. Şahinoğlu AH. Yoğun Bakım So- runları ve Tedavileri. 2. Baskı. Ankara: Türkiye Klinik- leri; 2003. p.9-16.

Yazar ve editörün aynı olduğu kitaplar için; Yazar(- lar)ın/editörün soyad(lar)ı ve isim(ler) inin başharf(ler) i, bölüm başlığı, kitap ismi, kaçıncı baskı olduğu, şehir, yayınevi, yıl ve sayfalar belirtilmelidir.

Türkçe kitaplar için;

Eken A. Cosmeceutical ingredients: drugs to cos- metics products. Kozmesötik Etken Maddeler. 1. Baskı.

Ankara: Türkiye Klinikleri; 2006. p.1-7.

İletişim:

Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fa- kültesi Dergisi Editörlüğü,

Avşar Yerleşkesi, KAHRAMANMARAŞ e posta: tipfak@ksu.edu.tr, ogungor@ksu.edu.tr Tel: 0 344 30 03 408

Format for books;

Initials of author’s names and surnames, chapter title, editor’s name, book title, edition, city, publisher, date and pages.

Example;

Underwood LE, Van Wyk JJ. Normal and aberrant growth. In: Wilson JD, Foster DW,eds. Wiliams’ Text- book of Endocrinology. 1st ed. Philadelphia: WB Saun- ders; 1992. p.1079-138.

Format for books of which the editor and author are the same person; Initials of author(s)’ editor(s)’ names and surnames chapter title, book title, edition, city, publisher, date and pages.

Example;

Solcia E, Capella C, Kloppel G. Tumors of the exoc- rine pancreas. Tumors of the Pancreas. 2nd ed. Was- hington: Armed Forces Institute of Pathology; 1997.

p.145-210.

Communication:

Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fa- kültesi Dergisi Editörlüğü,

Avşar Yerleşkesi, KAHRAMANMARAŞ e posta: tipfak@ksu.edu.tr, ogungor@ksu.edu.tr Tel: 0 344 30 03 408

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xiii KSÜ Tıp Fak Der 2020;15(3): i-xiv KSU Medical Journal 2020;15(3) : i-xiv

Yıl / Year: 2020 Cilt / Volume: 15 Sayı / Number: 3

Contents İÇİNDEKİLER

1.

Sayfa

7.

Sayfa

14.

Sayfa

37.

_Sayfa

40.

_Sayfa

54.

_Sayfa

47.

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22.

_Sayfa

Hidrojen Sülfür, Karbon Monoksit ve Nitrik Oksidin Sıçanlarda Pentilentetrazol İndüklü Nöbetler Üzerindeki Etkileri

The Effects of Hydrogen Sulfide, Carbon Monoxide and Nitric Oxide on Pentylenetetrazole-Induced Seizures in Rats Ezgi EROĞLU, Çiğdem ÇENGELLİ ÜNEL, Nuşin HARMANCI, Zuhal KALTUŞ, Cansu KILIÇ, Hatice

DOĞAN, Rabiye ALTINBAŞ, Kevser EROL Kronik Hepatit B Virüs Enfeksiyonu Olan Hastalarda Hepatit A Virüs Seroprevalansı

Hepatitis A Virus Seroprevalence in Patients with Chronic Hepatitis B Virus Infection

Sedef Zeliha ÖNER, Emine TÜRKOĞLU

Postmenopozal Osteoporozlu Kadınlarda Kinezyofobinin Yaşam Kalitesi Üzerine Etkisi

The Effect of Kinesiophobia on Quality of Life in Women with Postmenopausal Osteoporosis

Türkan TURGAY, Pınar GÜNEL KARADENİZ

Pulmoner Tromboemboli Şüphesi Olan Hastalarda Derin Ven Trombozu Tanısında İndirekt Bilgisayarlı Tomografi Venografi ile Renkli Doppler Ultrasonografi Bulgularının Karşılaştırılması

The Comparison of Color Doppler Ultrasonography and Indirect Computer Tomography Venography for the Diagnosis of Deep Venous Thrombosis in Patients with Suspected Pulmonary Thromboembolism

Betül GÜNEY, Mustafa GÜLEÇ Pan Antibiyotik Dirençli Pseudomonas (P.aeruginosa)

ve Stenotrophomonas’lara (S. maltophilia) Karşı Son Seçenek Ajanlardan Biri Olan Kolistin (Colistin)’in In Vitro Etkinliğinin Araştırılması

Investigation of In Vitro Effectiveness Of Colistin, An End-Option Agent Against Pan Antibiotic Resistant Pseudomonas (P.aeruginosa) and Stenotrophomonas (S.

maltophilia)

Murat TÜRKEN, Şahin YAZTÜRK, Mustafa YILMAZ, Merve YILMAZ BOZOĞLAN

Muş İli ve İlçelerindeki Hastanelerde Görev Yapan Hemşirelerin Sigara İçme Durumlarının Değerlendirilmesi

Evaluation of Smoking Status of Nurses Working In Hospitals In Mus Province and Districts

Leyla SEZGİN, Edibe PİRİNÇCİ

Entübasyona Hemodinamik Yanıtı Önlemede Remifentanil, Fentanil, Esmolol, Lidokain, ve Amiodaronun Etkilerinin Karşılaştırılması

Comparison of The Effects of Remifentanil, Fentanyl, Esmolol, Lidocaine, and Amiodarone in Preventing Hemodynamic Response to Intubation

Özlem ÖNER, Emel YILDIZ

Lateral Epikondilitte Fizik Tedavi ve Steroid Enjeksiyonunun Etkinliğinin Karşılaştırılması

A Comparison of The Effectiveness of Steroid Injection and Physical Therapy in Lateral Epicondylitis

Pınar MAZLUM MACİT, Gonca SAĞLAM, Akın ERDAL

Araştırma Makaleleri (Research Articles)

30.

_Sayfa

Korunmuş Ejeksiyon Fraksiyonu ve Diyastolik Disfonksiyonu Olan Hastalarda Kardiyak Dissenkroni Varlığı ve Kalp Yetmezliği Semptomları Üzerine Olan Etkisi

Presence of Cardiac Dyssyncrony and Its Effect on Heart Failure Symptoms’in Patients With Preserved Ejection Fractions and Diastolic Dysfunctions

Oya İMADOĞLU, Korhan SOYLU, Sabri DEMİRCAN

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82.

_Sayfa

88.

_Sayfa

94.

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100.

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105.

_Sayfa

109.

_Sayfa

112.

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116.

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Yenidoğan Yoğunbakım Ünitesinde Gelişimsel Bakım Developmental Care in the Neonatal Intensive Care Unit Serap KAYNAK, Hatice BAL YILMAZ, Zümrüt BAŞBAKKAL, Figen YARDIMCI

Plasenta Akreata; Geçmişten Bugüne Öyküsü Placenta Accreta; Hıstory From Past to Present Sezen KOÇARSLAN

Tiroid Nodülleri ve Nodüllere Yaklaşım Thyroid Nodules and Approach to Nodules

İrfan KARA, Muhammed Gazi YILDIZ, İsrafil ORHAN

Tekrarlayan Pseudomonas Tonsilitinin Nadir Ama Önemli Bir Nedeni: Yaygın Değişken İmmün Yetmezlik A Rare But Important Cause of Recurrent Pseudomonas Tonsillitis: Common Variable Immunodeficiency

Gökhan AYTEKİN, Fatih ÇÖLKESEN, Eray YILDIZ ,Şevket ARSLAN

Dev Vokal Proçes Granülomu Olan Hastanın Anestezik Yönetimi

Anesthetic Management of a Patient with Giant Vocal Process Granuloma

Ömer Faruk BORAN, Mahmut ARSLAN, Aykut URFALIOĞLU, Gözen ÖKSÜZ, Bora BİLAL, Selman SARICA, Feyza ÇALIŞIR

Postpartum Pons Kanaması Sonrası Gelişen Fisher 1.5 Sendromu

Fisher’s One and A Half Syndrome Developed After Postpartum Pons Hemorrhage

Raikan BÜYÜKAVCI, Hatice KübraYILDIRIM, Meral Kırmızı BİNGÖL

Palatin Tonsilin Epidermoid Kisti: Olgu Sunumu ve Literatürün Gözden Geçirilmesi

Epidermoid Cyst of the Palatine Tonsil: A Case Report and Literature Review

Ayşe Nur UĞUR KILINÇ

Keratinize Mukoza Eksikliği Olan İmplant Bölgelerinin Otojen Yumuşak Doku Grefti İle Ogmentasyonu Augmentation of Implant Sites with Insufficient Keratinised Mucosa by Autogenous Soft Tissue Grafting

Nazife HAMURCU, Samet TUNÇ, Kemal BİNİCİ, Deniz ÇETİNER

xiv KSÜ Tıp Fak Der 2020;15(3): i-xiv

KSU Medical Journal 2020;15(3) : i-xiv

Proton Pompa İnhibitörlerinin Uzun Dönem Kullanımlarındaki Etkileri

Effects of Proton Pump Inhibitors on Long-Term Use Murat İSPİROĞLU, Kadir GİŞİ, Bülent KANTARÇEKEN

76.

_Sayfa

İnme Hastalarında Çift Yönlü Görev Aktivitesinin Etkinliği

The Efficacy of Dual Task Activity In Stroke Patients Derya Tuba BAL, Tuba Tülay KOCA, Ejder BERK, Burhan Fatih KOÇYİĞİT, Vedat NACİTARHAN

Non Steroid Antiinflamatuar İlaç Kullanan Her Hastada Gastrik Profilaksi Gerekli mi?

Is Gastric Prophylaxis Necessary in Every Patient Using Non-Steroidal Anti-İnflammatory Drugs?

Kadir GİŞİ, Murat İspiroglu, Bülent KANTARÇEKEN

60.

_Sayfa

69.

_Sayfa

Derlemeler (Reviews)

Olgu Sunumları (Case Reports)

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KSU Medical Journal 2020;15(3) : 1-6

Araştırma Makalesi (Research Article)

The Effects of Hydrogen Sulfide, Carbon Monoxide and Nitric Oxide on Pentylenetetrazole-Induced Seizures in Rats

Hidrojen Sülfür, Karbon Monoksit ve Nitrik Oksidin Sıçanlarda Pentilentetrazol İndüklü Nöbetler Üzerindeki Etkileri

Ezgi EROĞLU¹, Çiğdem ÇENGELLİ ÜNEL¹, Nuşin HARMANCI¹, Zuhal KALTUŞ¹, Cansu KILIÇ¹, Hatice DOĞAN², Rabiye ALTINBAŞ¹, Kevser EROL³

Abstract

Objective: The present study aimed to investigate the anticonvulsant effects of bioactive gas mediator’s hydrogen sulfide (H2S), carbon monoxide (CO) and nitric oxide (NO) in pentylenetetrazole (PTZ)-induced convulsions in rats.

Material and Methods: Eighty male Wistar-Albino rats randomly divided into ten groups. Convulsions were induced by administering 60 mg/kg PTZ intraperitonally (i.p). Diazepam (1 and 2 mg/kg), sodium hydrosulfide (NaHS, 5 and 10 mg/kg), CO releasing molecule-2 (CORM-2, 5 and 10 mg/kg), L-arginine (LARG, 30 and 100 mg/kg) and L-NG-Nitro arginine methyl ester (L-NAME, 30 mg/kg) were administered 30 minutes after PTZ. Seizure latency, seizure duration and seizure score were evaluated. Data were analyzed by the Kruskal Wallis test followed by posthoc analyses with Tukey. Any p value <0.05 was considered statistically significant.

Results: NaHS (10 mg/kg) significantly reduced seizure duration and seizure in comparison with PTZ similar to diazepam (2 mg/kg), but it did not cause any significant change in seizure latency. Other agents did not significantly change seizure latency, seizure duration, and seizure score compared to PTZ.

Conclusion: NaHS may be protective in PTZ-induced seizures. More research is needed to investigate the mechanisms underlying this effect.

Keywords: Carbon monoxide, Epilepsy, Hydrogen Sulfide, Nitric Oxide, Seizures

Yazışma Adresi: Ezgi EROĞLU ESOGÜ Tıp Fakültesi Tıbbi Farmakoloji AD, Meşelik Kampüsü, 26480 Eskişehir Tlf:

05056942126 Mail: ezgbzkrt@gmail.com

ORCID No (Sırasıyla): 0000-0002-9878-3431; 0000-0001-7680-0141; 0000-0002-5777-2162; 0000-0003-2281-1712, 0000- 0003-1100-9417; 0000-0002-9616-8910; 0000-0003-2535-0480; 0000-0002-8808-6616

Özet

Amaç: Sıçanlarda pentilentetrazol (PTZ) ile tetiklenen konvülsiyonlarda biyoaktif gaz mediyatörler hidrojen sülfür (H₂S), karbon monoksit (CO) ve nitrik oksit (NO)’in antikonvülzan etkilerinin araştırılması amaçlanmıştır.

Gereç ve Yöntemler: Seksen erkek Wistar-Albino sıçan rastgele on gruba ayrılmıştır. Konvülsiyonlar, intraperitoneal olarak verilen 60 mg/kg PTZ ile tetiklendi. PTZ’den 30 dakika önce diazepam (1 ve 2 mg/kg), sodyum hidrosülfit (NaHS, 5 ve 10 mg/kg), CO salan molekül-2 (CORM-2, 5 ve 10 mg/kg), L-arginin (LARG, 30 ve 100 mg / kg) ve L-N^G-Nitro arjinin metil ester (L-NAME, 30 mg/kg) uygulandı. Nöbet latensi, nöbet süresi ve nöbet skoru kör iki gözlemci tarafından değerlendirildi.

Veriler Kruskal Wallis testi ve ardından Tukey ile analiz edildi. P değeri <0.05 olması istatistiksel olarak anlamlı kabul edildi.

Bulgular: NaHS (10 mg/kg) nöbet süresini ve skorunu diazepam (2 mg/kg) ile benzer şekilde PTZ’ye göre anlamlı ölçüde azaltırken nöbet latensinde anlamlı bir değişikliğe neden olmadı. Diğer ajanlar, nöbet latensi, nöbet süresi ve nöbet skorunu PTZ’ye göre anlamlı şekilde değiştirmedi.

Sonuç: NaHS (10 mg/kg) PTZ’ye bağlı nöbetlerde koruyucu olabilir. Bu etkinin altında yatan mekanizmaların araştırılması için daha fazla çalışmaya ihtiyaç duyulmaktadır.

Anahtar Kelimeler: Epilepsi, Hidrojen Sülfür, Karbon monoksit, Nitrik oksit, Nöbetler

¹Eskişehir Osmangazi Üniversitesi, Tıp Fakültesi, Tıbbi Farmakoloji Anabilim Dalı, Eskişehir, Türkiye

²Hatay Mustafa Kemal Üniversitesi, Tıp Fakültesi, Fizyoloji Anabilim Dalı, Hatay, Türkiye

3Bahçeşehir Üniversitesi, Tıp Fakültesi, Tıbbi Farmakoloji Anabilim Dalı, İstanbul, Türkiye Geliş tarihi: 29.01.2020 Kabul tarihi: 13.03.2020 DOI: 10.17517/ksutfd.681282

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MATERIALS AND METHODS

Eighty adult male Wistar rats (8-10 weeks old, weighing 180- 220 g) were used for the current experiments. They were housed in cages in a controlled room with 12/12 light dark cycle, temperature of 20-22°C and relative humidity of 65%- 70%. The study was performed in accordance with the guidelines for the care and use of laboratory animals approved by the Local Ethical Committee of Eskisehir Osmangazi Uni- versity (25.06.2019/745). PTZ, diazepam, NaHS, CORM-2, LARG and L-NAME were dissolved in saline and PTZ inje- cted 30 min after the last treatment with all agents according to de Oliveira et al. (18). A known anxiolytic drug, diazepam, was used as a positive control. Rats were randomly assigned into ten groups (n=8): PTZ group (60 mg/kg, i.p.), diazepam (1 mg/kg, i.p.)+PTZ group, diazepam (2 mg/kg, i.p.)+PTZ group, NaHS (5 mg/kg, i.p.)+PTZ group, NaHS (10 mg/kg, i.p.)+PTZ group, CORM (5 mg/kg, i.p.)+PTZ group, CORM (10 mg/kg, i.p.) and PTZ group, LARG (30 mg/kg, i.p.) and PTZ group, LARG (100 mg/kg, i.p.)+PTZ group, L-NAME (30 mg/kg, i.p.)+PTZ group. After PTZ injection, all rats were placed in a glass observation box and PTZ-induced seizure score, seizure latency, seizure duration were recorded for 30 min through direct observation by two blind investi- gators unaware of the groups. Behavioral seizures were rated according to the following Racine’s scale (19) as described previously with the following stages: (0) no abnormality; (1) Mouth and facial movements; (2) Head nodding; (3) Forelimb clonus; (4) Rearing; (5) Rearing and falling.

All data were expressed as mean±SEM. Statistical analysis was performed using IBM SPSS software version 21.0. The Shapiro-Wilk normality test was performed to verify the distribution of values in the Gaussian curve. Normality was not verified for the variables and thus, the nonparametric Kruskal-Wallis test followed by posthoc analyses with Tukey test used. P <0.05 was considered statistically significant.

RESULTS

It was shown that all treatment agents did not increase seizure latency significantly (Figure 1).

It was found that NaHS (10 mg/kg) considerably lowered the seizure duration considerably. On the other hand, the other substances were ineffective in terms of lowering seizure duration (Figure 2).

The seizure score was also found significantly lower in NaHS (10 mg/kg) than in PTZ groups. NaHS (5 mg/kg), CORM-2 (5 and 10 mg/kg), LARG (30 and 100 mg/kg) and L-NAME (30 mg/kg) had no effect (Figure 3).

INTRODUCTION

Epilepsy is a chronic disease characterized by recurrent seizures over a long period of time and loss of consciousness that often occurs during these seizures (1). It is one of the most common neurological disorders affecting 70 million people worldwide (2). Epilepsy causes clinical symptoms such as memory impairment, distraction and other cogniti- ve disorders in 30-40% of patients (3). The primary aims of epilepsy treatment are to prevent seizures, to avoid adverse effects, and to facilitate patients to have active lives (4). Des- pite the variety of these drugs available for the treatment of epilepsy, pharmacological approaches cannot control seizures in all cases (5). However, many antiepileptic drugs used in the treatment may have interactions with some important drugs or drug groups such as antibiotics, anticoagulants, oral contraceptives, salicylates, cimetidine and isoniazid (6). The- refore, all these conditions make it necessary to develop more rational methods in the treatment of epilepsy.

Animal models of seizures and epilepsy are crucial to increase our understanding of the underlying mechanisms of epileptogenesis and the clinical effects of novel antiepileptic drugs (7). Pentylentetrazole (PTZ), bicyclic tetrazole deriva- tive, is characterized by high bioavailability and rapid distribution after intraperitoneal (i.p.) injection and blocks γ-a- minobutyric acid (GABA)-mediated transmission (8). PTZ has been used comprehensively to induce seizures at higher doses in animal models (9).

Hydrogen sulfide (H₂S), carbon monoxide (CO) and nitric oxide (NO) are characterized as bioactive gas mediators that have been investigated during the past 20 years for their roles in human physiology (10). These gasotransmitters have different protective effects against oxidative stress which are related to their neuropsychiatric functions (11, 12). It was shown that the endogenous CO system is protective against brain damage induced by recurrent febrile seizures (13). In addition it was indicated that the pathways for hydrogen sulfide biosynthesis may be targets for antiepileptic strategies in poststroke epilepsy treatment (14). There are some contro- versial results about NO effects on convulsions (15-17). Thus, the aim of this study was to investigate the possible anti-convulsant effects of H₂S, CO and NO in PTZ-induced epilepsy model.

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Figure 1. Comparison of the study groups regarding seizure latency. The effects of diazepam and other groups on the seizure latency were compared.

PTZ: Pentylenetetrazole, Dia1: Diazepam 1 mg/kg, Dia2:Diazepam 2 mg/kg, NaHS5: Hydrogen sulfide donor 5 mg/kg, NaHS10: Hydrogen sulfide donor 10 mg/kg, CORM5: CO donor 5 mg/kg, CORM10: CO donor 10 mg/kg, LARG30: L-arginine 30 mg/kg, LARG100: L-arginine 100 mg/kg, LNAME30;

L-nitroarginine methy ester 30 mg/kg. (**:p <0.01 vs. PTZ)

Figure 2. Comparison of the study groups regarding seizure duration. The effects of diazepam and other groups on seizure duration were compared.

L-nitroarginine methy ester 30 mg/kg. (*:p<0.05 vs. PTZ)

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DISCUSSION

In the present study, it was shown that diazepam and H₂S do- nor NaHS significantly increased seizure latency compared to PTZ alone group whereas the remaining agents showed no effect. In addition, NaHS, similar to diazepam, lowered seizure duration of the rats. On the other hand, the other substances did not yield a significant effect when compared with that of PTZ alone group. Finally, all the agents but diazepam and NAHS failed to affect seizure score. Diazepam is a benzodiazepine class agent known for its anxiolytic, muscle relaxant and anticonvulsant effects, and is frequently used in emergency departments, especially in convulsions (20). In this study it was used as a positive control and was shown to be protective against PTZ seizures at a dose of 2 mg/kg. H₂S, CO and NO are gas molecules that are naturally produced and metabolized in the body acting as mediators in physiological situations in the emergence of diseases (21). These mediators provide protection against reactive oxygen and nitrogen species which are among the main causes of neuroinflammation. Therefore, it has been suggested that they play a protective role in various neurodegenerative diseases (22).

Although it has been suggested that gas neurotransmitters may also have effects on epilepsy studies regarding its beneficial effects are limited (23).

H₂S is a gas transmitter that has demonstrated vital biological effects in various physiological events including insu- lin release, blood pressure, cytoprotection, muscle relaxation and in the pathophysiology of various diseases such as inf-

lammation, hypertension, atherosclerosis, diabetes, myocar- dial infarction, Alzheimer’s and Parkinson’s diseases (24,25).

It has been shown that H₂S can provide inhibitory/excitatory balance in neurotransmission and regulate the activities of targets in seizures such as ion channels and NMDA recep- tors. However, information based on the mechanism of action of H₂S in seizures is limited (26, 27). In our study, it was observed that NaHS reduced seizure latency at both doses (5 and 10 mg/kg). However, it was found that NaHS (10 mg/kg), significantly reduced the seizure duration. In addition, the average of seizure score was remarkably lower in NaHS (10 mg/kg) group than in PTZ group According to this result, NaHS (10 mg/kg) was able to protect against PTZ-induced seizures.

Although CO is well known regarding its toxicity, it has beneficial biological effects in controlled doses and plays a role as a molecular messenger in various physiological pro- cesses of the nervous system (28). Various studies indicated that carbon monoxide has anti-inflammatory (29), antiproli- ferative (30), antiatherogenic (31), antihyperalgesic (32) and antiapoptotic effects (33). CORM-2 molecules are capable of carrying CO to tissues and cells (34). Studies have shown that heme-oxygenase enzyme, which catalyzes biosynthesis of carbon monoxide in the central nervous system, plays a protective role in various pathologies such as cerebrovascular diseases, pain and Alzheimer’s and Parkinson’s diseases (35).

CORM-A1 molecule, another carbon monoxide-releasing agent, has been found to be protective in neonatal vascular

Figure 3. Comparison of the study groups regarding seizure score. The effects of diazepam and other groups on seizure score were compared.

L-nitroarginine methy ester 30 mg/kg. (**:p <0.01 vs. PTZ)

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damage due to epileptic seizure (36). According to our literature review, there has been no report about the effects of CORM-2 molecules and CO molecule on seizures. It is thought that it may have effects on seizures due to its protective properties in the nervous system. However, in our study, it was seen that CORM-2 did not change the seizure latency at a dose of 10 mg/kg and increased the duration of the seizure similar to the PTZ group. It was observed that the averages of seizure score of CORM-2 at both 5 and 10 mg/kg dose were close to each other. Therefore, we did not observe any effect of CORM-2 in PTZ-induced seizures.

It has been suggested that NO may play a role in epilepsy and epileptogenesis due to the second messenger, neuromodulator and neurotransmitter roles in the central nervous system and NO has anti- or pro-convulsive properties, de- pending on the seizure model, the dosage of pharmacological agents in the experiments and the route of drug administ- ration (37). L-NAME has been shown to be proconvulsant in PTZ-induced seizures at doses of 10 and 40 mg/kg (38).

LARG and L-NAME did not change the seizure latency relative to the PTZ group in this study. Although it has been seen that L-NAME (30 mg/kg) decreased the seizure duration compared to PTZ group, but the difference was not statistically significant. The mean seizure score was also found to be high in both LARG and L-NAME groups.

In conclusion, our study showed that NaHS may have protective effects on PTZ-induced convulsions. However, these data are not yet sufficient to prove the antiepileptic effects of NaHS as a drug. More studies are needed that focus on the anticonvulsant effects of this agent in other animal species, as well as to obtain more information about its anticonvulsant effects

Acknowledgments

This study was supported by Eskişehir Osmangazi Uni- versity Scientific Research Projects Commission with the project code 2019/11D05. This study was presented as a pos- ter presentation in 25th National Congress of Turkish Phar- macology Society 4th -7th November 2019/Kusadasi/Turkey.

Conflict of Interest and Financial Status: Our study has not been financed by an institution and institution. In this study, there is no conflict of interest among the authors on any subject.

REFERENCES

1. Stafstrom CE, Carmant L. Seizures and epilepsy: an overview for neuroscientists. Cold Spring Harb Perspect Med. 2015;5(6):

a022426.

2. Singh A, Trevick S. The Epidemiology of Global Epilepsy.

Neurol Clin. 2016;34(4):837-47.

3. Laxer KD, Trinka E, Hirsch LJ, Cendes F, Langfitt J, Delanty N, et al. The consequences of refractory epilepsy and its treatment.

Epilepsy Behav. 2014;37:59-70.

4. Newton RW. When is drug treatment not necessary in epilepsy?

Factors that should influence the decision to prescribe. J R Soc Med. 2004;97(1):15-9.

5. Lazarini-Lopes W, Do Val-da Silva RA, da Silva-Junior RMP, Le- ite JP, Garcia-Cairasco N. The anticonvulsant effects of cannabi- diol in experimental models of epileptic seizures: from behavior and mechanisms to clinical insights. Neurosci Biobehav Rev.

2020 Apr;111:166-182. doi: 10.1016/j.neubiorev.2020.01.014.

6. Johannessen SI, Landmark CJ. Antiepileptic drug interactions - principles and clinical implications. Curr Neuropharmacol.

2010;8(3):254-67.

7. Loscher W. Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs. Seizure. 2011;20(5):359-68.

8. Samokhina E, Samokhin A. Neuropathological profile of the pentylenetetrazol (PTZ) kindling model. Int J Neurosci.

2018;128(11):1086-96.

9. Li B, Wang L, Sun Z, Zhou Y, Shao D, Zhao J, et al. The anticonvulsant effects of SR 57227 on pentylenetetrazole-induced seizure in mice. PLoS One. 2014;9(4):e93158.

10. Farrugia G, Szurszewski JH. Carbon monoxide, hydrogen sulfide, and nitric oxide as signaling molecules in the gastrointesti- nal tract. Gastroenterology. 2014;147(2):303-13.

11. Shefa U, Yeo SG, Kim MS, Song IO, Jung J, Jeong NY, et al. Role of Gasotransmitters in Oxidative Stresses, Neuroinflammation, and Neuronal Repair. Biomed Res Int. 2017;2017:1689341.

12. Shefa U, Kim D, Kim MS, Jeong NY, Jung J. Roles of Ga- sotransmitters in Synaptic Plasticity and Neuropsychiat- ric Conditions. Neural Plast. 2018 May;2018:1824713. doi:

10.1155/2018/1824713. eCollection 2018

13. Yang ZX, Qin J, Du JB, Chang XZ, Han Y. Effect of endogenous heme oxygenase-carbon monoxide on brain damage induced by recurrent febrile seizures. Zhonghua Er Ke Za Zhi.

2005;43(4):252-5.

14. Luo Y, Wu PF, Zhou J, Xiao W, He JG, Guan XL, et al. Aggrava- tion of seizure-like events by hydrogen sulfide: involvement of multiple targets that control neuronal excitability. CNS Neuros- ci Ther. 2014;20(5):411-9.

15. Herberg LJ, Grottick A, Rose IC. Nitric oxide synthesis, epileptic seizures and kindling. Psychopharmacology (Berl).

1995;119(1):115-23.

16. Osonoe K, Mori N, Suzuki K, Osonoe M. Antiepileptic effects of inhibitors of nitric oxide synthase examined in pentylenetetrazol-induced seizures in rats. Brain Res. 1994;663(2):338-40.

17. Buisson A, Lakhmeche N, Verrecchia C, Plotkine M, Boulu RG.

Nitric oxide: an endogenous anticonvulsant substance. Neuro- report. 1993;4(4):444-6.

18. de Oliveira CC, de Oliveira CV, Grigoletto J, Ribeiro LR, Funck VR, Grauncke AC, et al. Anticonvulsant activity of beta-caryop- hyllene against pentylenetetrazol-induced seizures. Epilepsy Behav. 2016;56:26-31.

19. Kang X, Shen X, Xia Y. Electroacupuncture-induced attenuation of experimental epilepsy: a comparative evaluation of acupoints and stimulation parameters. Evid Based Complement Alternat Med. 2013;2013:149612. doi: 10.1155/2013/149612.

20. Dhir A, Rogawski MA. Determination of minimal steady-state plasma level of diazepam causing seizure threshold elevation in rats. Epilepsia. 2018;59(5):935-44.

21. Polhemus DJ, Lefer DJ. Emergence of hydrogen sulfide as an endogenous gaseous signaling molecule in cardiovascular disease.

Circ Res. 2014;114(4):730-7.

22. Panthi S, Manandhar S, Gautam K. Hydrogen sulfide, nitric oxide, and neurodegenerative disorders. Transl Neurodegener.

2018;7:3.

(20)

EROĞLU ve ark.

23. Leffler CW, Parfenova H, Jaggar JH, Wang R. Carbon monoxide and hydrogen sulfide: gaseous messengers in cerebrovascular circulation. J Appl Physiol. 2006;100(3):1065-76.

24. Hu LF, Lu M, Hon Wong PT, Bian JS. Hydrogen sulfide:

neurophysiology and neuropathology. Antioxid Redox Signal.

2011;15(2):405-19.

25. Kimura H, Nagai Y, Umemura K, Kimura Y. Physiological roles of hydrogen sulfide: synaptic modulation, neuroprotection, and smooth muscle relaxation. Antioxid Redox Signal. 2005;7(5- 6):795-803.

26. Abe K, Kimura H. The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci. 1996;16(3):1066-71.

27. Tang G, Wu L, Wang R. Interaction of hydrogen sulfide with ion channels. Clin Exp Pharmacol Physiol. 2010;37(7):753-63.

28. Ismailova A, Kuter D, Bohle DS, Butler IS. An Overview of the Potential Therapeutic Applications of CO-Releasing Molecules.

Bioinorg Chem Appl. 2018;2018:8547364.

29. Otterbein LE. Carbon monoxide: innovative anti-inflammatory properties of an age-old gas molecule. Antioxid Redox Signal.

2002;4(2):309-19.

30. Otterbein LE, Soares MP, Yamashita K, Bach FH. Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol. 2003;24(8):449-55.

31. Fredenburgh LE, Merz AA, Cheng S. Haeme oxygenase signal- ling pathway: implications for cardiovascular disease. Eur Heart J. 2015;36(24):1512-8.

32. Joshi HP, Kim SB, Kim S, Kumar H, Jo MJ, Choi H, et al. Nano- carrier-mediated Delivery of CORM-2 Enhances Anti-allody- nic and Anti-hyperalgesic Effects of CORM-2. Mol Neurobiol.

2019;56(8):5539-54.

33. Al-Huseini LM, Aw Yeang HX, Hamdam JM, Sethu S, Alhu- meed N, Wong W, et al. Heme oxygenase-1 regulates dendritic cell function through modulation of p38 MAPK-CREB/ATF1 signaling. J Biol Chem. 2014;289(23):16442-51.

34. Crespy D, Landfester K, Schubert US, Schiller A. Potential pho- toactivated metallopharmaceuticals: from active molecules to supported drugs. Chem Commun (Camb). 2010;46(36):6651- 62.

35. Queiroga CS, Vercelli A, Vieira HL. Carbon monoxide and the CNS: challenges and achievements. Br J Pharmacol.

2015;172(6):1533-45.

36. Zimmermann A, Leffler CW, Tcheranova D, Fedinec AL, Parfe- nova H. Cerebroprotective effects of the CO-releasing molecule CORM-A1 against seizure-induced neonatal vascular injury.

Am J Physiol Heart Circ Physiol. 2007;293(4):2501-7.

37. Banach M, Piskorska B, Czuczwar SJ, Borowicz KK. Nitric oxide, epileptic seizures, and action of antiepileptic drugs. CNS Neurol Disord Drug Targets. 2011;10(7):808-19.

38. Jelenkovic A, Jovanovic M, Ninkovic M, Maksimovic M, Bo- konjic D, Boskovic B. Nitric oxide (NO) and convulsions induced by pentylenetetrazol. Ann N Y Acad Sci. 2002;962:296-305.

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KSÜ Tıp Fak Der 2020;15(3): 7-13

7

Araştırma Makalesi (Research Article)

Investigation of In Vitro Effectiveness Of Colistin, An End-Option Agent Against Pan Antibiotic Resistant Pseudomonas (P.aeruginosa) and Stenotrophomonas (S.

maltophilia)

Pan Antibiyotik Dirençli Pseudomonas (P.aeruginosa) ve

Stenotrophomonas’lara (S. maltophilia) Karşı Son Seçenek Ajanlardan Biri Olan Kolistin (Colistin)’in In Vitro Etkinliğinin Araştırılması

Murat TÜRKEN¹, Şahin YAZTÜRK², Mustafa YILMAZ¹, Merve YILMAZ BOZOĞLAN³

Özet

Amaç: Son yıllarda nozokomial infeksiyon hastalıklarının artışı dikkat çekicidir. Buna rağmen literatürlerde pan-antibiyotik dirençli bakterilerin yol açtığı infeksiyonların tedavisinin eldeki antibiyotiklerle neredeyse imkansız olduğu belirtilerek yeni antibiyotiklerin geliştirilmesine ve arayışına gereksinim olduğu bildirilmiştir.

Dirençli infeksiyonlarda, karşımıza çıkan; Klebsiella spp., Enterobacter spp., Pseudomonas aeruginosa, Acinetobacter spp. ve son yıllarda önemi giderek artan Stenotrophomonas maltophilia’lar hatırlanır. Bu mikroorganizmalar, yaygın olarak kullanılan antibiyotiklere karşı değişik mekanizmalarla direnç geliştirmekte ve neden oldukları infeksiyonların tedavisinde büyük sorunlar yaşanmaktadır.

Bu çalışmanın amacı Fırat Üniversitesi Tıp Fakültesi Mikrobiyoloji Anabilim Dalı Laboratuvarına gönderilen örneklerden izole edilen, 57 Pseudomonas aeruginosa ve 10 adet Stenotrophomonas maltophilia suşunun kolistin ve diğer antibiyotiklere duyarlılığı açısından incelenmesidir.

Gereç ve Yöntemler: İzolatların tanımlanmasında konvansiyonel bakteriyolojik yöntemler kullanılmıştır. Suşların antimik- robiyallare duyarlılıkları disk difüzyon ve E-test yöntemiyle çalışıldı. Kolistin duyarlılığı ise E-testi yöntemi kullanılarak tespit edilmiştir.

Bulgular: Pseudomonas aeruginosa ve Stenotrophomonas maltophilia türlerinin disk düfüzyon yönteminde kullanılan Aztreo- nam (ATM), Seftazidim (CAZ), Sefoksitin (FOX), Sefotaksim (CTX), İmipenem (IPM), Meropenem (MEM), Amikasin (AK), Gentamisin (CN),Trimetoprim-sülfametoksazol (SXT), Siprofloksasin (CİP), Sefuroksim (CXM), Ampisilin (Amp),Amoksi- silin klavulanat (Amc) disklerinin tamamına dirençli olduğu saptandı. Ayrıca E-testinde kullanılan Piperasilin+tazobaktam (TZP), Tikarsilin klavunic asid (TLc), Amikasin (AK), CİP, IPM, MEM, CAZ, Ofloksasin (OFX) striplerine karşıda invitro olarak dirençli bulundu. Kolistin ile yapılan E-testinde ise, Pseudomonas aeruginosa %15,7 duyarlı, Stenotrophomonas maltop- hilia ise hepsi dirençli bulunmuştur.

Sonuç: İzole edilen kökenlerde oldukça yüksek oranda antimikrobiyal direnç, hastanemizde bu kökenlerin neden olduğu in- feksiyonların önemli bir sorun haline geldiğinin bir işaretidir. Kolistin’in nefrotoksik ve nörotoksik yan etkileri de göz önüne alınarak dikkatle kullanılabileceği düşünülmektedir.

Anahtar Kelimeler:Nozokomial infeksiyonlar, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Kolistin, E-testi.

1Fırat Üniversitesi, Tıp Fakültesi, Tıbbi Mikrobiyoloji Anabilim Dalı, Elazığ, Türkiye

2Siverek Halk Sağlığı Müdürlüğü, Şanlıurfa, Türkiye

3Elazığ İl Sağlık Müdürlüğü, Elazığ, Türkiye

Geliş tarihi: 05.03.2019 Kabul tarihi: 01.05.2020 DOI: 10.17517/ksutfd.536070

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TÜRKEN ve ark.

Abstract

Objective: Number and type of the antibacterial medicines which are used for nosocomial infection are increasing in recent years. Although this situation, in literature it is pointed out that the infections caused by bacteria which are resistant against pan-antibiotic, can not be treated by the present antibiotics. For this reason new antibiotics must be developed.

When we think about the resistant gram-negative bacteria, we can remember some of them such as Klebsiella, Enterobacter, Pseudomonas aeruginosa, Acinetobacter and the most important one Stenotrophomonas maltophilia. These microorganisms mostly resistant against present antibiotics and their cure is very difficult.

The aim of this study is to examine 57 Pseudomonas aeruginosa and 10 Stenotrophomonas maltophilia strains, which are isolated from samples sent to Fırat University Faculty of Medicine, Department of Microbiology, in terms of susceptibility to colistin and other antibiotics.

Material and Methods: Conventional bacteriological methods were used to identify the isolates. The susceptibility of strains to antimicrobials was studied by disk diffusion and E-test method. The sensitivity of colistin was determined using the E-test method.

Results: Pseudomonas aeruginosa and Stenotrophomonas maltophilia species were found to be resistant to all Aztreonam (ATM), Ceftazidime (CAZ), Cefoxitin (FOX), Cefotaxime (CTX), Imipenem (IPM), Meropenem (MEM), Amikacin (AK), Gentamycin (CN), Trimethoprim-sulfamethoxazole (SXT), Ciprofloxacin (SXT) ), Cefuroxime (CXM), Ampicillin (Amp), Amoxicillin clavulanate (Amc)discs used in disc diffusion method. In addition, Piperacillin + tazobactam (TZP), Tikarsilin clavunic acid (TLc), Amikacin (AK), CIP, IPM, MEM, CAZ, Ofloxacin (OFX) strips were found to be in vitro resistant in vitro.

In the E-test with colistin, Pseudomonas aeruginosa was found to be 15.7% sensitive and Stenotrophomonas maltophilia were all resistant.

Conclusion: The high rate of antimicrobial resistance in the isolated origins is a sign that the infections caused by these origins have become a major problem in our hospital. It is thought that colistin can be used with care considering the nephrotoxic and neurotoxic side effects.

Keywords: Nosocomial infection, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Colistin, E-test.

Yazışma Adresi: Murat TÜRKEN Fırat Üniversitesi, Tıp Fakültesi, Tıbbi Mikrobiyoloji Anabilim Dalı, Elazığ, Türkiye Telefon: 0505 950 7728 e-mail: muratturkenmur@gmail.com

ORCID No (Sırasıyla):1200-6627-1792-1996, 1200-6627-1792-1996, 1200-6627-1792-1996, 1200-6627-1792-1996